title: In vivo manipulation of γ9(+) T cells in the common marmoset (Callithrix Jacchus) with phosphoantigen and effect on the progression of respiratory melioidosis.
abstract: Burkholderia pseudomallei is a dangerous human pathogen. Phosphoantigens specifically the target primate specific γ9(+)δ2(+) T cells subset and some have been developed as potential immunotherapeutics. Previously, we demonstrated that, when stimulated with the phosphoantigen CHDMAPP, γ9(+)δ2(+) T cells aid in the killing of intracellular B. pseudomallei bacteria. Moreover, we found that common marmoset (Callithrix Jacchus) γ9(+) T cells increase in frequency and respond to the phosphoantigen CHDMAPP and/or B. pseudomallei, in combination with IL-2, in a similar manner to human γ9(+)δ2(+) T cells. Here we evaluate the efficacy of the phosphoantigen CHDMAPP, in combination with IL-2, as a therapy against B. pseudomallei infection, in vivo. We found that the previous studies predicted the in vivo responsiveness of γ9(+) T cells to the CHDMAPP+IL-2 treatment and significant expansion of the numbers of peripheral and splenic γ9(+) T cells were observed. This effect was similar to those reported in other primate species treated with phosphoantigen. Furthermore, splenocytes were retrieved 7 days post onset of treatment, restimulated with CHDMAPP or heat-killed B. pseudomallei and the cultured γ9(+) T cells demonstrated no reduction in IFN-γ response when CHDMAPP+IL-2 animals were compared to IL-2 only treated animals. Using an established model of B. pseudomallei infection in the marmoset, we assessed the potential for using phosphoantigen as a novel immunotherapy. The CHDMAPP treatment regime had no effect on the progression of respiratory melioidosis and this was despite the presence of elevated numbers of γ9(+) T cells in the spleen, liver and lung and an increased proportion of IFN-γ(+) cells in response to infection. We therefore report that the common marmoset has proven a good model for studying the effect in vivo of γ9(+) T cell stimulation; however, γ9(+) T cells have little or no effect on the progression of lethal, respiratory B. pseudomallei infection.
authors.affiliation: Biomedical Sciences Dept, Defence Science and Technology laboratory (DSTL) Porton Down, Salisbury, United Kingdom.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Laws
authors.forename: Michelle
authors.initials: M
authors.lastname: Nelson
authors.forename: Cecile
authors.initials: C
authors.lastname: Bonnafous
authors.forename: Helene
authors.initials: H
authors.lastname: Sicard
authors.forename: Christopher
authors.initials: C
authors.lastname: Taylor
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Salguero
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Atkins
authors.forename: Petra C F
authors.initials: PC
authors.lastname: Oyston
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Rowland
mesh_terms: D000818:Animals; D016957:Burkholderia pseudomallei / Q000276:immunology*; D002144:Callithrix; D005434:Flow Cytometry; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology; D008554:Melioidosis / Q000188:drug therapy / Q000276:immunology / Q000662:veterinary*; D008992:Monkey Diseases / Q000188:drug therapy* / Q000276:immunology*; D010750:Phosphoproteins / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D007376:Interleukin-2; D010750:Phosphoproteins; D007371:Interferon-gamma